This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The significance of our findings is that we have developed and implemented a system to quantifiably evaluate the fitness advantages or disadvantages imparted by specific envelope glycoprotein sequences. This was done either over the course of infection within a single individual or in transmission pairs. We have also begun to develop in vitro model system to define the molecular determinants of fitness in transmission and in replicative assays. Our result should help to refine the development of strategies to vaccinate against the HIV-1 glycoprotein by identifying rational targets with pathogenetic significance.